| 陈伟圣,孙棱,祖宇瑶,等.基于分子对接方法研究山核桃叶黄酮单体对痛风关节炎中NLRP3炎症信号通路的作用[J].浙江中医药大学学报,2019,43(6):605-612. |
| 基于分子对接方法研究山核桃叶黄酮单体对痛风关节炎中NLRP3炎症信号通路的作用 |
| Research of Effect of Flavonoids Monomers from Carya Cathayensis Leaves on Gouty Arthritis through NLRP3 Inflammasomes Signaling Pathway Based on Molocular Docking |
| DOI：10.16466/j.issn1005-5509.2019.06.020 |
| 中文关键词: 山核桃叶 分子对接 黄酮单体 NLRP3通路 靶点蛋白 N-乙酰基转移酶 机制 |
| 英文关键词: Carya cathayensis leaves molecular docking flavonoids monomers NLRP3 pathway target protein N-acetyltransferase mechanism |
| 基金项目:浙江省公益性技术应用研究计划(2017C33107) |
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| 中文摘要: |
| [目的]基于分子对接方法研究山核桃叶总黄酮中的单体成分对痛风关节炎中寡聚化结构域样受体3(nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain containing 3，NLRP3)炎症信号通路的作用机制。[方法]以NLRP3炎症通路信号传递蛋白为受体，山核桃叶醇提取物中的5种黄酮单体汉黄芩素、白杨素、小豆蔻明、球松素查尔酮、松属素为配体，通过ChemBioDraw软件预测黄酮单体类药性质，利用AutoDock软件进行配体-受体分子模拟对接，以结合能(binding energy，BE)和抑制常数(inhib constant，IC)作为评分标准，筛选出作用靶点蛋白。[结果] N-乙酰基转移酶、NLRP3炎性体、核因子-κB(nuclear factor-κB，NF-κB)、硫氧还蛋白互作蛋白(thioredoxin-interacting protein，TXNIP)等炎性蛋白均与山核桃叶总黄酮中单体成分结合较好，提示山核桃叶总黄酮的作用具有多靶点性，而各单体的作用靶点之间存在差异，球松素查尔酮主要抑制热休克蛋白(heat shock protein，HSP)、硫氧还蛋白2(thioredoxin 2，TRX2)活性，以及天冬氨酸半胱氨酸特异性蛋白酶-1(cysteinyl aspartate specific proteinase-1，caspase-1)前体的酶解，侧重于抑制NLRP3通路激活过程；汉黄芩素、白杨素、松属素和小豆蔻明则主要抑制NLRP3和N-乙酰基转移酶1活性、caspase-1前体的酶解、白细胞介素-1β(interleukin-1β，IL-1β)与配体的结合，作用于NLRP3炎性体及其激活过程，其中多种黄酮单体与N-乙酰基转移酶对接较为突出，推测N-乙酰基转移酶可作为痛风性关节炎的治疗靶点。[结论]山核桃叶总黄酮中单体成分具有一定的抗痛风性关节炎的作用，其作用机制可能与NLRP3炎性体及其激活过程相关。 |
| 英文摘要: |
| [Objective] To observe the anti-inflammatory effect of flavonoids monomers from Carya cathayensis leaves on gouty arthritis based on nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain containing 3(NLRP3) inflammasomes signaling pathway by molecular docking technology. [Methods] The signal transduction proteins of NLRP3 inflammatory pathway were collected as a receptor; and flavonoids extracted from Carya cathayensis leaves, including wogonin, chrysin, cardamom, pinstrobin Chalcone and pinocembrin, whose drug-like properties were predicted by ChemBioDraw, were used as a ligand. The ligand-receptor molecular docking was calculated by AutoDock, and the target proteins were screened according to the binding energy(BE) and inhib constant(IC). [Results] N-acetyltransferase, NLRP3, nuclear factor-κB(NF-κB), thioredoxin-interacting protein(TXNIP) and other inflammatory proteins are well combined with flavonoids from Carya cathayensis leaves，indicate the multi-targeting of total flavonoids in Carya cathayensis leaves, but the target proteins of the flavonoids are different. It shows pinstrobin Chalcone mainly inhibit the activation process，such as heat shock protein(HSP), thioredoxin 2(TRX2) activity, enzymolysis of pro-cysteinyl aspartate specific proteinase-1(pro-caspase-1). While wogonin, chrysin, cardamom and pinocembrin mainly inhibit caspase-1 activity, binding of interleukin-1β(IL-1β) to ligand, NLRP3 and N-acetyltransferase 1 activity, all act on the NLRP3 inflammasome and its activation process. At the same time, a variety of flavonoid monomers docked with N-acetyltransferase are more prominent，it is speculated that N-acetyltransferase could be used as a therapeutic target for gouty arthritis. [Conclusion] Flavonoid monomers from Carya cathayensis leaves have anti-gouty arthritis effects, and its mechanism is correlated with NLRP3 inflammasome axis. |
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